As early as 1970s, the study of pharmacokinetics was very mature, and its sign was that the disposal process of any drug in the body could be described by mathematical formula. This also strongly promoted the development of pharmacodynamics research, and made clinicians have a detailed understanding of the relationship between blood drug concentration and pharmacodynamics. People have long recognized that in order to maintain the stability of drug efficacy, it is necessary to maintain a stable effective blood concentration, which can also reduce the side effects of drugs. By studying the disposal process of different drugs in vivo in detail, unique metabolic kinetic parameters were obtained, which laid the foundation for specific medication methods. On this basis, we can calculate what the first loading dose should be, the interval between drugs or the rate of continuous administration, and how long it is expected to take to reach the steady-state blood concentration. However, complex mathematical operations hinder the clinical application of pharmacokinetics, so pharmacokinetics is only a tool for researchers most of the time. This situation changed completely with the popularization of computers, especially the increasing popularity of computer microchips in the 1980s, which led to the emergence of injection pumps with complex real-time computing capabilities. When the pharmacokinetic parameters of some drugs are written into the computer chip, a special injection pump which can target-controlled infusion of specific drugs is produced.

Target-controlled infusion has the following characteristics:

1, which can quickly reach the required anesthesia depth (plasma target concentration or effect room target concentration), and can continuously maintain or adjust this concentration according to needs.

2. You can choose the target blood concentration or the effect room concentration, and the clinical effect is similar, but the latter is faster than the former in inducing and waking up.

3. Because the population parameters are used for individuals, there is individual deviation between the target concentration and the actual blood drug concentration, but this deviation is far less than the difference of individual drug response, so it will not obviously affect the use. Moreover, the target concentration is directly proportional to the actual plasma concentration, which is very beneficial to guide and control the depth of anesthesia.

4. Target-controlled infusion is simple. As long as the drug used, the required target concentration, the patient's age, sex and weight are determined, everything will be done by a computer pump, and the target concentration can be adjusted according to the patient's reaction. The basic requirements of general anesthesia are: even if the patient's consciousness disappears, there is no or only mild stress response to harmful stimuli (surgical stimuli), muscle relaxation can meet the needs of surgery, and postoperative analgesia is satisfactory. Muscle relaxation drugs can easily achieve muscle relaxation.

1, basic requirements of drug collocation: Only when sedatives and hypnotics are combined with analgesic anesthetics can total intravenous anesthesia be well completed. The collocation choice of these two drugs is varied, which should be determined according to the characteristics of the operation, the patient's situation and the experience of the anesthesiologist.

2, familiar with the interaction between drugs: compound drugs will produce drug interaction, addition, synergy and antagonism. Only by paying special attention to the first two functions can we master the depth of anesthesia. See relevant chapters for details.

3. Medication principle: The minimum dose of sedative and hypnotic drugs should be used to ensure the patient's consciousness to disappear during the operation, supplemented by sufficient dose of analgesic drugs to weaken or eliminate the patient's stress response to the operation.

4. Adjustment of drugs: When sedatives and hypnotics are combined with narcotic analgesics, the depth of anesthesia should be adjusted as needed during operation. Generally, sedative and hypnotic drugs are not easy to reduce the awareness of prevention, but the dosage of anesthetic and analgesic drugs should be adjusted to maintain a satisfactory depth of anesthesia. If propofol is combined with remifentanil, the dose of remifentanil should be adjusted. If propofol is combined with ketamine, the dosage of propofol should be adjusted.

5. Management principles and methods

It is necessary to quickly reach the required plasma concentration or effect room concentration, so a loading dose is given first, and the specific dose is: Bolus = Ct' Vd Ct' Vd Ct is the target concentration, and Vd is the distribution volume of the drug. In order to maintain the stability of drug concentration, it is necessary to supplement the elimination amount of injected drugs from the body: elimination = CT ′ Cl, and Cl is the clearance rate of drugs in the blood. In addition to eliminating the amount, the drug should be slowly distributed to other chambers in the body, so that the drug concentration in the blood will be reduced. Distribution (for two atrioventricular models): transfer = CT ′ k12 ′ e-k 2 1 vdtk12 and k 21are the drug distribution rates between two atrioventricular models, respectively, and t is a given time. Make the blood drug concentration reach the requirement quickly and keep stable. TCI infusion pump and manual infusion set all follow this principle. For example, in order to make the plasma concentration of propofol reach 3ug/ml quickly and keep it stable, it is necessary to adopt a three-step medication method: first, intravenous injection of 1.5mg/kg, then infusion of 10min at 10min, and the second infusion of/kloc-at 8 mg/kg/h.

It is best to use a special TCI pump for administration, which is convenient and simple. If not, an ordinary injection pump can be used, but the dosage and speed of administration according to body weight corresponding to the target concentration should be referred to. Generally, the method of constant-speed administration is not adopted, because it takes at least 4-5 half-lives to reach a stable blood concentration. Unless it is a drug with a very short half-life, such as remifentanil with t 1/2, the drug concentration can be considered to reach a steady state after 5 minutes. See relevant chapters for drug dosage.